P894: A PHASE II TRIAL TO EVALUATE THE EFFICACY OF DARATUMUMAB WITH DCEP IN RELAPSED/REFRACTORY MULTIPLE MYELOMA PATIENTS WITH EXTRAMEDULLARY DISEASE AFTER BORTEZOMIB BASED TREATMENT
Authors: J. M. Byun, C.-K. Min, K. Kim, S.-M. Bang, J.-J. Lee, J. S. Kim, S.-S. Yoon, Y. Koh
Journal: HemaSphere (2022)

Background: Extramedullary multiple myeloma (EMM) is an aggressive subentity of multiple myeloma (MM), characterized by the ability of a subclone to thrive and grow independent of the bone marrow microenvironment, resulting in a high-risk state associated with increased proliferation, evasion of apoptosis and treatment resistance. Despite improvement in survival for most patients with MM over recent decades, outcomes are generally poor when EMM develops. Thus, better understanding of the disease and more innovative therapeutic approaches are needed. Aims: To study the efficacy and safety of daratumumab in combination with dexamethasone, cyclophosphamide, etoposide and cisplatin (DCEP) Methods: This was a multi-center, prospective phase II study (ClinicalTrials.gov identifier: NCT04065308). A total of 33 patients older than 19 years with multiple myeloma according to IMWG, relapsed/refractory to bortezomib, and with EMM (short-axis ≥1cm by CT or PET-CT) were enrolled. As shown in the Figure, patients received 3 cycles of daratumumab in combination with DCEP, followed by daratumumab maintenance. The primary objective was complete response rate after 3 cycles of daratumumab with DCEP. The secondary objectives included: 1) overall response rates; 2) progression free survival (PFS); 3) overall survival; and 4) safety and toxicity profiles. Here we present the interim data of 24 patients. Results: The median age at MM diagnosis was 57 years (range 34-71) and 79.2% patients had EMM at diagnosis. There were 10 patients with t(4;14), 4 patients with del(17p) and 6 patients with t(14;16). There were 6 patients (25%) with ISS I disease, 10 (41.7%) with ISS II disease, and 8 (33.3%) with ISS III disease. The median number of prior lines of treatment was 3 (range 1-5), with all patients being exposed to bortezomib prior to enrollment. Also, 70.8% patients had prior exposure to carfilzomib, 87.5% to lenalidomide, and 50% to pomalidomide. There were 17/24 (70.8%) patients who completed 3 cycles: 3 showed CR; 2 showed VGPR; 11 showed PR and 7 with progressive disease as shown in the Figure. Six patients were able to complete the study protocol. For all patients the median PFS was 4 months, but for those who completed the study protocol the median PFS was not reached and all but 1 remained in remission until the data cut-off in 2022-Jan-31. Patients achieving PR or better response after cycle 3 showed significantly better PFS (6 vs 2 months, p<0.001) compared to those who didn’t. Most patients (22/24) underwent cyclophosphamide/etoposide/cisplatin dose reduction by 30% at cycle 1. One patient required further dose reduction at cycle 2. There was 1 patient who went off trial at D15 of cycle 1 according to attending physician’s decision and 2 patients who had to skip D22 daratumumab during cycle 1 due to thrombocytopenia. No patients required dexamethasone dose adjustments. During cycle 1, 12.5% showed anemia ≥grade 3, 25% showed thrombocytopenia ≥grade 3, 4.2% showed lymphopenia ≥grade 3, and 4 (16.7%) events of febrile neutropenia. During cycle 3, 5.3% showed anemia ≥grade 3, 10.5% showed thrombocytopenia ≥grade 3, while 15.8% showed lymphopenia ≥grade 3. The most common non-hematological adverse events was nausea (20.8%). Image:Summary/Conclusion: In conclusion, daratumumab in combination with DCEP showed overall response of 66.7% (CR 25%), and durable remission in 20.8% of the enrolled patients.